Stability of Olmesartan Medoxomil Tablets in Unit-Dose Packaging With Metformin Hydrochloride Tablets.

BACKGROUND: The widespread implementation of unit-dose packaging has improved medication adherence, particularly in elderly populations. However, potential physicochemical interactions between co-packaged drugs remain a concern. Therefore, the present study evaluated the stability of metformin hydrochloride (MET) tablets and olmesartan medoxomil (OLMMD) tablets (orally disintegrating tablet: OLMOD/standard tablet: OLM), including both brand name and generic products, when unit-dose packaged and stored under a high temperature and humidity (40°C, 75% RH) or room temperature for up to 28 days.  Methods: A visual inspection and HPLC quantification were used to assess the discoloration of MET and content of OLMMD.  Results: When MET1 (brand name) or MET2 (generic) was packaged with OLMOD1 (brand name), no discoloration or degradation was observed. However, with MET3 (generic), time-dependent pink discoloration occurred when co-packaged with OLMOD2 or OLMOD3 (generics). OLMMD content remained nearly 100% even in formulations inducing MET discoloration. Differences were attributed to excipient and manufacturing variability. Notably, OLMOD1 uniquely contained β-cyclodextrin, which may stabilize OLMMD via inclusion complexation. By contrast, MET discoloration may reflect hygroscopicity and variability in film-coating properties. Although pharmacological efficacy was unaffected due to preserved OLMMD stability and the harmless nature of MET discoloration, visual changes may reduce patient adherence. Thus, selecting stable combinations that avoid discoloration is important in clinical practice, especially for elderly or cognitively impaired patients. CONCLUSIONS: This study highlights the importance of excipient selection and formulation design in ensuring stability in unit-dose packaging. The development of compatibility guidelines and formulation reference lists is warranted to support safe co-packaging practices.